Inactivation of the LRP1 intracellular NPxYxxL motif in LDLR-deficient mice enhances postprandial dyslipidemia and atherosclerosis.

National Cholesterol Awareness Month Inactivation of the LRP1 Intracellular NPxYxxL Motif in LDLR-Deficient Mice Enhances Postprandial Dyslipidemia and Atherosclerosis

Impaired LDL Receptor-Related Protein 1 Translocation Correlates with Improved Dyslipidemia and Atherosclerosis in apoE-Deficient Mice

OBJECTIVE Determination of the in vivo significance of LDL receptor-related protein 1 (LRP1) dysfunction on lipid metabolism and atherosclerosis development in absence of its main ligand apoE. METHODS AND RESULTS LRP1 knock-in mice carrying an inactivating mutation in the NPxYxxL motif were crossed with apoE-deficient mice. In the absence of apoE, relative to LRP1 wild-type animals, LRP1 muta...

Sterol regulatory element-binding protein-1 determines plasma remnant lipoproteins and accelerates atherosclerosis in low-density lipoprotein receptor-deficient mice.

OBJECTIVE Sterol regulatory element-binding protein-1 (SREBP-1) is nutritionally regulated and is known to be a key transcription factor regulating lipogenic enzymes. The goal of this study was to evaluate the roles of SREBP-1 in dyslipidemia and atherosclerosis. METHODS AND RESULTS Transgenic mice that overexpress SREBP-1c in the liver and SREBP-1-deficient mice were crossed with low-density...

Low-Density Lipoprotein Receptor–Related Protein 1 Prevents Early Atherosclerosis by Limiting Lesional Apoptosis and Inflammatory Ly-6C Monocytosis Evidence That the Effects Are Not Apolipoprotein E Dependent

absence of apoE and LRP1 promoted atherogenesis more than did macrophage apoE deletion alone in both apoE-producing LDLR / mice ( 88%) and apoE / mice ( 163%). The lesions of both mouse models with apoE / LRP1 / macrophages had increased macrophage content. In vitro, apoE and LRP1 additively inhibit macrophage apoptosis. Furthermore, there was excessive accumulation of apoptotic cells in lesion...

Hepatic remnant lipoprotein clearance by heparan sulfate proteoglycans and low-density lipoprotein receptors depend on dietary conditions in mice.

OBJECTIVE Chylomicron and very low-density lipoprotein remnants are cleared from the circulation in the liver by heparan sulfate proteoglycan (HSPG) receptors (syndecan-1), the low-density lipoprotein receptor (LDLR), and LDLR-related protein-1 (LRP1), but the relative contribution of each class of receptors under different dietary conditions remains unclear. APPROACH AND RESULTS Triglyceride...